A number of diterpene alkaloids (DAs) and their derivatives have been investigated for curaremimetic activity. Their structure-activity relationships and the mechanisms of their action have been studied. Structural fragments of the DAs that are responsible for curaremimetic properties have been revealed. Among the compounds studied, nudicauline and lycaconitine are superior to the curaremimetic drugs melliktin and condelphine.Drugs interacting selectively with the H--cholinoreceptors of the central nervous system, the vegetative ganglia, and the neuromuscular synapses are widely used in experimental and practical medicine. The demand for drugs of this type with different action spectra and mechanisms is extremely great, since with their use it is possible to control many functions of the internal organs and to change the tonns of skeletal muscles and also to act on the processes involved in the interneuron transmission of excitation in the central nervous system.Diterpene alkaloids are of interest as objects in the search for new curaremimetic drugs with an enteral action, since, being tertiary amines, they are absorbed in the gastrointestinal tract, and, acting on the peripheral H-cholinoreceptors and freely penetrating through the blood-brain barrier, they exert an action on the central nervous system.Investigations performed as early as the 1950s-1960s have shown that such alkaloids from plants of the genus Delphinium as lycoctonine (delsine), delsemine, avadharidine, methyllycaconitine, condelphine, and elatine possess a pronounced curaremimetic action which is revealed on injection into the stomach [1-3].At the present time, methyllycaconitine hydriodide (melliktin/"mellictine") is being used in medicine as a curaremimetic in the treamaent of various neurological and other diseases connected with an increased tonus of the skeletal musculature [4]. The structural elements responsible for the curare-like activity of the lycoctonine alkaloids have been discussed in a review [3].In recent years, as the result of vigorous progress in the field of diterpene alkaloid chemistry, a large number of new compounds have been isolated and their structures have been determined. In view of this, we considered it desirable to carry out a search for new muscle relaxants, to study their structure-activity relationships and action mechanisms, and to determine the prospects of their use in practical medicine and biology.
SCREENING AND THE RELATIONSHIP BETWEEN CHEMICAL STRUCTURE AND CURAREMIMETIC ACTION AMONG DITERPENE ALKALOIDSWe have investigated a series of diterpenoid compounds isolated from plants of the genera Aconitum and Delphinium and based mainly on lycococtonine, heteratisine, atisine, hetisine, denudatine and veatchine skeletons, and their modified analogs.The results of the investigations showed that the capacity for exhibiting a muscle-relaxing action is possessed by alkaloids with various types of skeletons. The most active compounds were found among alkaloids with the lycoctonine skeleton, while atisine and hetera...